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Biomedical subjects

I R Edwards

Publications and source records attributed to I R Edwards.

At least 91 records · Page 5Linked to original sources

Studies on the copper and zinc content of the rat kidney after treatment with cisplatin.

The administration of cis-dichlorodiammine platinum II (cisplatin), at a dose of 5 mg/kg, subcutaneously (s.c.), to adult male Wistar rats, inhibited the normal accumulation of Cu and Zn in the kidneys. Cisplatin also produced a small increase in the concentration of Cu in the brain but had no significant effect on total Cu and Zn concentrations in the heart, thymus, liver, intestine, spleen, testes and muscle. Treatment of rats with 2 mg Cu2+/kg, intraperitoneally (i.p.), increased the renal Cu content whilst cisplatin pretreatment inhibited the uptake of Cu by the kidneys. The administration of cisplatin to the Cd2+-pretreated rat decreased the content of metallothionein-bound Cu in parallel with a reduction in total renal Cu content, but had no significant effect on the total renal content of Cd and Zn. Pretreatment with cisplatin decreased the subsequent uptake of Cd by 42% in the whole kidney and by 23% in the metallothionein fraction, but failed to reduce the Cd2+-induced accumulation of Cu in the kidneys. The significance of these observations in relation to the possible mechanism of the cisplatin-induced change in the Cu and Zn content of the kidney is discussed.

Animals↗

Pharmacokinetic projections for isoxicam and piroxicam in old and young subjects.

A single-dose pharmacokinetic study to determine the effect of age on the disposition of isoxicam and piroxicam was carried out on a group of old and a group of young subjects. Although there was no significant difference with either drug in the mean elimination half-time between the group of young and the group of old subjects, there was considerable individual variation. Steady-state levels were calculated to be three times as high in subjects with slow clearance as in those with more rapid clearance. Three weeks would be required with either drug to achieve steady-state drug levels in those subjects with slow drug-clearance.

Absorption↗

Interaction of platinum with metallothionein-like ligands in the rat kidney after administration of cis-dichlorodiammine platinum II.

After the administration of the anticancer drug cis-dichlorodiammine platinum II (cisplatin) to male rats, the Pt in the soluble fraction of the kidney is isolated, by gel filtration, in association with a high molecular weight component and a low molecular weight fraction. At 24 h, Pt is also recovered in a metallothionein-like fraction which elutes from Sephadex G-50 with a lower apparent molecular weight than endogenous (Cu, Zn)-thionein or Cd-thionein isolated from the kidneys of Cd2+-treated rats. None of these low molecular weight metal-binding fractions binds to Octyl Sepharose CL-4B. On DE-52 ion exchange chromatography, Cd-thionein is resolved into two isometallothioneins whereas the low molecular weight Pt-binding fraction is only partially purified and contains at least six components which elute at higher gradient concentrations than metallothionein. Pretreatment with Cd2+ which stimulates the synthesis of renal and hepatic metallothionein has no effect on the uptake and subcellular distribution of Pt in the liver and kidneys. Cisplatin treatment reduces the concentration of Cu and Zn in the renal metallothionein and other soluble protein fractions in the kidney. When administered to Cd2+-pretreated rats, cisplatin promotes the loss of Zn from the soluble protein fractions but causes the redistribution of Cd from the metallothionein to the high molecular weight fraction and fails to inhibit the Cd2+-induced accumulation of Cu in the kidneys and the binding of Cu to the soluble protein fractions. It is suggested that metallothionein probably does not have a significant role in the renal metabolism of Pt following the administration of cisplatin to rats.

Animals↗

Nutritional status of the social class groups.

There is a marked increase in mortality and morbidity with decreasing social class status so that the death rate of adult males in social class V is twice that of men in social class I. Differences in nutritional status between the social classes could account for this phenomenon. In this survey the nutritional status of 254 consecutive adult admissions to a teaching hospital was assessed by anthropometric and biochemical measurements and delayed hypersensitivity skin tests. No significant difference in nutritional status was detected between the five social class groups. There was no significant difference between the combined social class groups I and II compared with IV and V. A similar result was obtained with the same assessment of 167 fit adult individuals of comparable age and sex distribution living in the community. There is no significant difference in nutritional status between the social classes when they are well or ill and therefore the differences in mortality and morbidity in lower social classes are unlikely to be caused by inadequate nutrition.

Adolescent↗

cis-Platinum: subcellular distribution and binding to cytosolic ligands.

In the present experiments the tissue uptake and subcellular distribution of Pt were measured in the liver and kidney of rats injected intraperitonially with 5 mg cis-diamminedichloroplatinum (cis-DPP)/kg. The binding of Pt to cytosolic ligands was also investigated. In both the liver and kidney Pt concentration was maximal within 24 hr following cis-DDP injection. Thereafter the clearance was bimodal with a rapid phase of about 48 hr (with 60-70% clearance) followed by a slow incomplete phase. In the kidney relatively high concentrations of Pt were measured in the microsomal, lysosomal and mitochondrial fractions. But in the liver the higher levels were found in the microsomal and nuclear fractions. On average 62% (kidney) and 89% (liver) of the cellular Pt were localized in the cytosol. At 24 hr following cis-DDP injection, about 52% of cytosolic Pt was present as low molecular weight species (molecular weight less than 1000) and the remainder as protein-bound. About 25% was bound to a metallothionein-like protein in the liver as well as the kidneys. It is suggested that the high localization of cellular Pt in the cytosol and the presence of a high proportion as non-protein bound species may be important factors in relation to the therapeutic as well as the toxic effects of cis-DDP.

Acid Phosphatase↗

Microanalysis of platinum in biological media by graphite furnace atomic absorption spectroscopy.

An accurate method for the analysis of platinum in biological matrix is described. The method requires minimal sample handling and pretreatment prior to injection into the graphite furnace. It is reproducible, with average recovery of 97.7% platinum in biological matrix. The data presented also demonstrate that Fe in particular (also NaCl and HNO3) significantly depresses the atomic absorption signal of platinum. Standard addition calibration curves are therefore essential for determination of platinum in biological samples.

Humans↗

Solvent abuse.

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Adhesives↗

Once-daily dosing of timolol in hypertension: a controlled study.

Nine previously untreated patients with mild-moderate hypertension were included in a dose-ranging double-blind trial to determine the effectiveness of daily versus thrice daily timolol administration. In 8 patients control of blood pressure was equally effective though with significantly lower heart rate achieved in the once daily group. One patient was not satisfactorily controlled on the daily regimen demostrating that many but not all hypertensives can be controlled with daily administration of timolol.

Administration, Oral↗

Diazepam in immediate post-myocardial infarct period. A double blind trial.

One hundred and thirty-one male patients admitted to a coronary care unit with myocardial infarction, later confirmed, were randomly allocated to receive either 10 mg diazepam every six hours, or a matched placebo, for 48 hours. During this period, no differences were found between the treatment groups in the incidence of fatal or non-fatal tachyarrhythmias even when account was taken of differences in the severity of the initial infarct. Monitored blood pressure and heart rate data were comparable as were the patients' self-assessed anxiety levels and symptoms, except that drowsiness was more common in the patients treated with diazepam.

Adult↗